Anti-parallel β-sheet - a signature structure of the oligomeric amyloid-beta peptide
Résumé
Alzheimer's disease (AD) is linked to amyloid beta peptide (Aβ) misfolding. Studies demonstrate that the level of soluble Aβ oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms. Conformation-dependent antibodies have been developed to detect either Aβ oligomers or fibrils, suggesting that structural differences between these forms of Aβ exist. Using conditions which yield well-defined Aβ(1-42) oligomers or fibrils, we studied the secondary structure of these species by attenuated total reflection-FTIR spectroscopy. Whereas fibrillar Aβ was organized in a parallel β-sheet conformation, oligomeric Aβ displayed distinct spectral features, which were attributed to an anti-parallel β-sheet structure. We also noted striking similarities between Aβ oligomers spectra and those of bacterial outer membrane porins. We discussed our results in terms of a possible organization of the anti-parallel β-sheets in Aβ oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.
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